Document Detail


ETS gene fusions in prostate cancer.
MedLine Citation:
PMID:  19657377     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Chromosomal rearrangements that result in high level expression of ETS gene family members are common events in human prostate cancer. Most frequently, the androgen-activated gene TMPRSS2 is found fused to the ERG gene. Fusions involving ETV1, ETV4 and ETV5 occur less frequently but exhibit greater variability in fusion structure with 12 unique 5' fusion partners identified so far. ETS gene rearrangement seems to be a key event in driving prostate neoplastic development: the rearrangement occurs as an early event and continues to be expressed in metastatic and castration-resistant disease. However, ETS alterations seem insufficient on their own to induce cancer formation. No consistent associations are seen between the presence of ETS alteration and clinical outcome, with the possible exception that duplication of rearranged ERG, reflecting aneuploidy, is associated with poor outcome. Thus, factors other than ERG gene status may be the major determinants of poor clinical outcome. Expression signatures of prostate cancers containing the TMPRSS2-ERG fusion suggest involvement of beta-estradiol signaling, and reveal higher levels of expression of HDAC1 and ion channel genes when compared to cancers that lack the rearrangement. These observations suggest new therapeutic possibilities for patients harboring ETS gene fusions.
Authors:
Jeremy P Clark; Colin S Cooper
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Nature reviews. Urology     Volume:  6     ISSN:  1759-4820     ISO Abbreviation:  Nat Rev Urol     Publication Date:  2009 Aug 
Date Detail:
Created Date:  2009-08-06     Completed Date:  2010-04-19     Revised Date:  2014-02-19    
Medline Journal Info:
Nlm Unique ID:  101500082     Medline TA:  Nat Rev Urol     Country:  England    
Other Details:
Languages:  eng     Pagination:  429-39     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Gene Expression Regulation, Neoplastic / genetics
Humans
Male
Oncogene Proteins, Fusion / biosynthesis,  genetics*,  physiology
Prostatic Neoplasms / genetics*,  metabolism,  pathology
Proto-Oncogene Proteins c-ets / biosynthesis*,  genetics*,  physiology
Translocation, Genetic
Tumor Markers, Biological / biosynthesis*,  genetics*,  physiology
Grant Support
ID/Acronym/Agency:
G0501019//Medical Research Council; //Cancer Research UK
Chemical
Reg. No./Substance:
0/Oncogene Proteins, Fusion; 0/Proto-Oncogene Proteins c-ets; 0/TMPRSS2-ETS fusion protein, human; 0/Tumor Markers, Biological

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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